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BACKGROUND: The oleaginous yeast Rhodotorula toruloides is a promising chassis organism for the biomanufacturing of value-added bioproducts. It can accumulate lipids at a high fraction of biomass. However, metabolic engineering efforts in this organism have progressed at a slower pace than those in more extensively studied yeasts. Few studies have investigated the lipid accumulation phenotype exhibited by R. toruloides under nitrogen limitation conditions. Consequently, there have been only a few studies exploiting the lipid metabolism for higher product titers. RESULTS: We performed a multi-omic investigation of the lipid accumulation phenotype under nitrogen limitation. Specifically, we performed comparative transcriptomic and lipidomic analysis of the oleaginous yeast under nitrogen-sufficient and nitrogen deficient conditions. Clustering analysis of transcriptomic data was used to identify the growth phase where nitrogen-deficient cultures diverged from the baseline conditions. Independently, lipidomic data was used to identify that lipid fractions shifted from mostly phospholipids to mostly storage lipids under the nitrogen-deficient phenotype. Through an integrative lens of transcriptomic and lipidomic analysis, we discovered that R. toruloides undergoes lipid remodeling during nitrogen limitation, wherein the pool of phospholipids gets remodeled to mostly storage lipids. We identify specific mRNAs and pathways that are strongly correlated with an increase in lipid levels, thus identifying putative targets for engineering greater lipid accumulation in R. toruloides. One surprising pathway identified was related to inositol phosphate metabolism, suggesting further inquiry into its role in lipid accumulation. CONCLUSIONS: Integrative analysis identified the specific biosynthetic pathways that are differentially regulated during lipid remodeling. This insight into the mechanisms of lipid accumulation can lead to the success of future metabolic engineering strategies for overproduction of oleochemicals.

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRβ pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 μg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRβ as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRβ, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRβ pathway thereby influencing skeletal muscle development. [ABSTRACT FROM AUTHOR]

Pathological myopia (PM) is one of the leading causes of blindness, especially in Asia. To identify the genetic risk factors of PM, a two‐stage genome‐wide association study (GWAS) and replication analysis in East Asian populations is conducted. The analysis identified LILRB2 in 19q13.42 as a new candidate locus for PM. The increased protein expression of LILRB2/Pirb (mouse orthologous protein) in PM patients and myopia mouse models is validated. It is further revealed that the increase in LILRB2/Pirb promoted fatty acid synthesis and lipid accumulation, leading to the destruction of choroidal function and the development of PM. This study revealed the association between LILRB2 and PM, uncovering the molecular mechanism of lipid metabolism disorders leading to the pathogenesis of PM due to LILRB2 upregulation. [ABSTRACT FROM AUTHOR]

Background: Obesity is a major contributing factor to the formation of gallstones. As early identification typically results in improved outcomes, we explored the relationship between visceral lipid accumulation indicators and the occurrence of gallstones. Methods: This cross-sectional study involved 3,224 adults. The researchers employed multivariable logistic regression, smoothed curve fitting (SCF), threshold effects analysis, and subgroup analysis to examine the relationship between metabolic scores for visceral fat (METS-VF), waist circumference (WC), lipid accumulation products (LAP), and visceral adiposity index (VAI) and gallstones. A Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to identify key factors which were then used in the construction of a nomogram model. The diagnostic efficacy of this model in detecting gallstones was then determined using receiver operating characteristic curves. Results: Visceral lipid accumulation indicators were strongly linked to the likelihood of having gallstones. Specific saturation effects for METS-VF, WC, LAP, and VAI and gallstones were determined using SCF. The inflection points for these effects were found to be 8.565, 108.400, 18.056, and 1.071, respectively. Subgroup analyses showed that associations remained consistent in most subgroups. The nomogram model, which was developed using critical features identified by LASSO regression, demonstrated excellent discriminatory ability, as indicated by an area under the curve value of 0.725. Conclusions: Studies have shown that increases in METS-VF, WC, LAP, and VAI are linked to increased prevalences of gallstones. The nomogram model, designed with critical parameters identified using LASSO regression, exhibits a strong association with the presence of gallstones. [ABSTRACT FROM AUTHOR]

Practical Application To investigate the effect of bound phenolics extracts (BPEs) of jujube peel on relieving cadmium (Cd)‐induced toxicity and its mechanism, the behavioral deficits, lipid accumulation, and fatty acid synthesis‐related gene expression in Caenorhabditis elegans in Cd exposure group and BPEs improvement groups were determined and compared. The results showed that BPEs significantly improved Cd‐induced behavioral deficits in C. elegans, and no significant differences could be found in low‐dose (12.5 µg/mL) and high‐dose (100 µg/mL) BPEs improvement groups. The treatment of BPEs effectively improved intestinal injury and lipofuscin and lipid accumulation. Especially, oil red O staining intensity in C. elegans treated with BPEs at 50 µg/mL was reduced by 12.60%. BPEs significantly controlled the increase in content of C16:0, C16:1, C18:0, C18:1, and C18:2 induced by Cd by regulating the lipid accumulation in Escherichia coli OP50. Cd exposure induced lipid accumulation in C. elegans by upregulating oleic acid synthesis‐related gene expression in E. coli OP50. Furthermore, BPEs treatment significantly downregulated the fatty acid synthesis‐related gene expression in C. elegans and E. coli OP50. This research could reveal the mechanism of BPEs of jujube peel in relieving Cd‐induced toxicity and provide a theoretical basis for the development of functional foods rich in polyphenols.Jujube peel, a by‐product of jujube processing, is usually discarded due to its coarse texture. However, jujube peel has been proven to possess abundant polyphenols, polysaccharides, and cyclic adenosine phosphate. In addition, in our previous research, bound phenolics extracts (BPEs) of jujube peel were found to perform better in lowering lipid accumulation than that of free phenolics extracts. This study further investigate the effect of BPEs of jujube peel on relieving Cd‐induced toxicity and its mechanism on the base of our previous research. It could realize the comprehensive utilization of by‐products of jujube processing. [ABSTRACT FROM AUTHOR]

Microalgae are considered to be a promising and prospective source of lipids for the production of biocomponents for conventional liquid fuels. The available sources contain a lot of information about the cultivation of biomass and the amounts and composition of the resulting bio-oils. However, there is a lack of reliable and verified data on the impact of fuel blends based on microalgae biodiesel on the quality of the emitted exhaust gas. Therefore, the main objective of the study was to present the emission characteristics of a compression-ignition engine fuelled with a blend of diesel fuel and biodiesel produced from the lipids accumulated in the biomass of a heterotrophic culture of Schizochytrium sp. The final concentrations of microalgal biomass and lipids in the culture were 140.7 ± 13.9 g/L and 58.2 ± 1.1 g/L, respectively. The composition of fatty acids in the lipid fraction was dominated by decosahexaenoic acid (43.8 ± 2.8%) and palmitic acid (40.4 ± 2.8%). All parameters of the bio-oil met the requirements of the EN 14214 standard. It was found that the use of bio-components allowed lower concentrations of hydrocarbons in the exhaust gas, ranging between 33 ± 2 ppm and 38 ± 7 ppm, depending on the load level of the engine. For smoke opacity, lower emissions were found in the range of 50–100% engine load levels, where the observed content was between 23 ± 4% and 53 ± 8%. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of fatty acid transport protein 1 (FATP1) in decapod crustaceans is still poorly understood. In this study, we cloned the FATP1 cDNA from the mud crab Scylla paramamosain, identified its sequence features and tissue distribution pattern and analyzed its roles in lipid metabolism in vivo. We found that FATP1 is involved in long-chain polyunsaturated fatty acid metabolism and deposition in crustaceans, which provides new information for understanding the function of FATP1 in invertebrates. In mammals, fatty acid transport protein 1 (FATP1) plays important roles in cellular uptake and activation of long-chain fatty acid (LCFA), especially in processes of transportation, oxidation and triacylglycerol synthesis. However, the role of FATP1 in invertebrates, especially decapod crustaceans, is still poorly understood. In this study, the cDNA of a FATP1 gene from a decapod crustacean, mud crab Scylla paramamosain, was cloned and functionally characterized. The FATP1 gene encoded a polypeptide consisting of 643 amino acids that exhibits all the typical features of the FATP family and shares high homology with the other FATP orthologs of crustaceans. The relative mRNA expression levels of FATP1 were observed to be higher in metabolically active tissues such as hepatopancreas, stomach and gill than in other crab parts. Knockdown of the FATP1 mRNA in vivo significantly reduced triacylglycerols and total lipid levels in the hepatopancreas, accompanied by an increase in the expression of genes related to fatty acid transportation, allocation and hydrolysis, including long-chain acyl-CoA synthetase 3/4 (ACSL3/4) and carnitine palmitoyl transferase 1 (CPT1), and a decrease in the expression of genes related to fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the hepatopancreas. Furthermore, increased dietary n-3 long-chain polyunsaturated fatty acid (LC-PUFA) levels resulted in the up-regulation of the FATP1 expression in the hepatopancreas, accompanied by an increase in LC-PUFA content, especially eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), in both polar (PLs) and neutral lipids (NLs) in the hepatopancreas and muscles of crabs. These findings suggested that the FATP1 gene identified in S. paramamosain might play important roles in regulating long-chain fatty acid metabolism and deposition in crustaceans. [ABSTRACT FROM AUTHOR]

Phospholipid: diacylglycerol acyltransferase (PDAT) is crucial in triacylglycerol (TAG) synthesis as it represents the final rate-limiting step of the acyl-CoA-independent acylation reaction. PDAT not only regulates lipid synthesis in plants, but also plays an important function in improving stress tolerance. In this study, the full-length coding sequence (CDS) of XsPDAT1, totaling 2022 base pairs and encoding 673 amino acids, was cloned from Xanthoceras sorbifolium. The relative expression of XsPDAT1 was significantly and positively correlated with oil accumulation during seed kernel development; there were some differences in the expression patterns under different abiotic stresses. Transgenic Arabidopsis thaliana plants overexpressing XsPDAT1 were obtained using the Agrobacterium-mediated method. Under low-temperature stress, the transgenic plants exhibited a smaller decrease in chlorophyll content, a smaller increase in relative conductivity, and a larger increase in POD enzyme activity and proline content in the leaves compared with the wild type. Additionally, lipid composition analysis revealed a significant increase in unsaturated fatty acids, such as oleic (C18:1) and linoleic (C18:2), in the seeds of transgenic plants compared to the wild type. These results suggest that XsPDAT1 plays a dual role in regulating the ratio of fatty acid composition and low-temperature stress in plants. [ABSTRACT FROM AUTHOR]

Background: Rosa canina L. (rosehip) is used worldwide in traditional medicine as a plant with medicinal properties. However, its anti-obesity effects are not fully explained on a transcriptional level. Methods: In the present work, the 3T3-L preadipocytes were utilized to explore the impact of R. canina fruit extract (RCE) on the cellular and molecular pathways involved in adipocyte hypertrophy. Results: Obtained results showed the ability of RCE to reduce lipid overloads in hypertrophic adipocytes associated with the down-regulation of mRNA expressions of adipogenic transcription factors such as PPARγ, C/EBPα, and SREBP-1c as well as genes involved in lipid biosyntheses such as FAS, LPL, and aP2. Moreover, obesity-associated oxidative stress (antioxidant enzyme activities and ROS generation) and inflammation were ameliorated in RCE-treated hypertrophic adipocytes. The mRNA and protein levels of adipokines such as leptin, resistin, and adiponectin were restored to more favorable levels. Conclusions: Rosa canina fruit might be a valuable source of phytochemicals in preventing obesity and obesity-related metabolic complications. [ABSTRACT FROM AUTHOR]

Dendrobine (DDB), an alkaloid isolated from the Chinese herb Dendrobium, has antioxidant and anti-inflammatory effects; however, whether DDB reduces oleic acid (OA)-induced lipid accumulation remains unclear. OA-induced lipid accumulation model of HepG2 cells were treated with DDB. Cellular lipid deposition was assessed by Oil Red O (ORO) staining and triglyceride and total cholesterol detection. RNA-Sequencing (RNA-seq), biological function analysis, and transcription factor (TFs) prediction were combined to identify key TF in the DDB-treated OA model. Finally, the roles of FOS and METTL14 were examined using a DDB-induced lipid accumulation model. DDB inhibited OA-induced lipid accumulation. We identified 895 differentially expressed genes (DEGs) that were mainly enriched in various biological processes of lipid synthesis and transport. Four transcription factors (SOX9, MLXIPL, FOS, and JUN) associated with lipid metabolism and FOS levels in the OA-induced lipid accumulation model after DDB treatment had the greatest changes in expression change. Overexpression of FOS alleviates the inhibitory effect of DDB on OA-induced lipid accumulation. METTL14 is a target gene of FOS, and simultaneous interference with METTL14 in cells with high FOS expression restored the alleviating effect of DDB on lipid accumulation. DDB alleviated OA-induced lipid accumulation by inhibiting the FOS/METTL14 pathway. [ABSTRACT FROM AUTHOR]

Background: The standardized extract ofmilk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)- induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms. Methods: A model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (ReactiveOxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides. Results: PM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II. Conclusion: Silibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Nonalcoholic fatty liver disease (NAFLD), a chronic metabolic disorder marked by excessive lipid deposition, represents a considerable health burden with no established efficacious treatment strategy. Quinoa (Chenopodium quinoa Willd.), valued for its health benefits, is replete with flavonoid bioactives. The aims of this work are to isolate and purify flavonoids from quinoa whole grain that can intervene in NAFLD and to elucidate some of the underlying mechanisms.Chenopodium quinoa Willd. flavonoids (CQWF) were obtained successfully through an optimized ultrasonic extraction methodology, followed by isolation and purification utilizing macroporous resin D101. The study then explored the therapeutic potential of CQWF and its eluted fractions in models emulating NAFLD conditions: an in vitro fatty liver cell model induced by oleic acid (OA) and palmitic acid (PA) in the HepG2 and BEL‐7402 cell lines, and an in vivo high‐fat diet (HFD)‐induced NAFLD model in C57BL/6N mice. The findings revealed a comprehensive mitigating effect of CQWF30 on NAFLD, manifesting in reduced intracellular lipid accumulation in steatotic hepatocytes and a concerted downregulation of key lipid metabolism genes, CD36 and FASN. Administration of CQWF30 reduced triglyceride (TG) levels in both the cellular model and the livers of HFD‐fed mice. It also reduced serum concentrations of TG, total cholesterol (T‐CHO), low‐density lipoprotein cholesterol (LDL‐C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), while increasing high‐density lipoprotein cholesterol (HDL‐C) in the mice.These results highlighted the promising therapeutic capacity of CQWF, particularly CQWF30. This research advances the exploration and utilization of flavonoids derived from quinoa whole grain, providing innovative dietary intervention strategies for NAFLD. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The experiment aim of this study was to investigate the effects of alfalfa water extract and haw⁃ thorn leaf water extract on fat accumulation in HepG2 cells and their antioxidant activities. The adipose accumulation model of HepG2 cells was induced by sodium oleate in vitro. Alfalfa extract、hawthorn leaf extract、alfalfa extract-Hawthorn leaf extract combination were used to intervene, and cell viability was determined by MTT method. The distribution of lipid droplets was observed by oil red O staining. The contents of triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione oxidase (GSH-Px) and total antioxidant capacity (T-AOC) were determined by bioassay. The results showed that the combination of alfalfa extract and hawthorn leaf extract (6∶4) could reduce the number of lipid droplets induced by oleic acid in HepG2 cells, and reduce the con⁃ tents of TG and TC in the cells.The combination of LC (6∶4) can significantly reduce the increase in the number of lipid droplets and the contents of TG and TC caused by sodium oleate induction in HepG2 cells, and has antioxidant capacity, and can increase the activity of SOD and GSH-Px enzymes and total antioxidant capacity in cells (P<0.01), decreased the production of MDA (P<0.05). In conclusion, the combination of alfalfa extract and hawthorn leaf extract can significantly inhibit the accumulation of HepG2 fat induced by sodium oleate, which is superior to the monomers of alfalfa extract or hawthorn leaf extract，at the same time it can improve the endogenous antioxidant capacity of cells. [ABSTRACT FROM AUTHOR]

Scenedesmus sp. is a species of the Scenedesmus genus within the phylum Chlorophyta, commonly found as a planktonic algal species in freshwater and known for its rapid growth rate. This study employs room-temperature, atmospheric-pressure plasma mutagenesis for the breeding of Scenedesmus sp., utilizing transcriptomic analysis to investigate the biosynthesis mechanism of triglycerides. Further analysis of differentially expressed genes in transcriptome by measuring the macroscopic biological indicators of mutant and original algal strains. The findings of the study suggest that the mutant strain's photosynthesis has been enhanced, leading to improved light energy utilization and CO2 fixation, thereby providing more carbon storage and energy for biomass and lipid production. The intensification of glycolysis and the TCA (tricarboxylic acid) cycle results in a greater shift in carbon flux towards lipid accumulation. An elevated expression level of related enzymes in starch and protein degradation pathways may enhance acetyl CoA accumulation, facilitating a larger substrate supply for fatty acid production and thereby increasing lipid yield. [ABSTRACT FROM AUTHOR]

Disrupted lipid metabolism is a characteristic of gliomas. This study utilizes an ultrastructural approach to characterize the prevalence and distribution of lipids within gliomas. This study made use of tissue from IDH1 wild type (IDH1-wt) glioblastoma (n = 18) and IDH1 mutant (IDH1-mt) astrocytoma (n = 12) tumors. We uncover a prevalent and intriguing surplus of lipids. The bulk of the lipids manifested as sizable cytoplasmic inclusions and extracellular deposits in the tumor microenvironment (TME); in some tumors the lipids were stored in the classical membraneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vasculature have lipid deposits in their lumen and vessel walls; this lipid could have shifted in from the tumor microenvironment or have been produced by the vessel-invading tumor cells. Lipid excess in gliomas stems from disrupted beta-oxidation and dysfunctional oxidative phosphorylation pathways. The implications of this lipid-driven environment include structural support for the tumor cells and protection against immune responses, non-lipophilic drugs, and free radicals. [ABSTRACT FROM AUTHOR]

[Display omitted] • ASIC1 facilitates atherosclerosis via impeding lipophagy. • ASIC1 promotes RIP1 phosphorylation. • ASIC1-RIP1 interaction contributes to defective autophagy flux. • ASIC1/RIP1 facilitates lipid accumulation via inhibiting lipophagy. • ASIC1/RIP1 may be a novel target for atherosclerotic treatment. Atherosclerosis, a major contributor to cardiovascular disease, remains a significant health concern worldwide. While previous research has shown that acid-sensing ion channel 1 (ASIC1) impedes macrophage cholesterol efflux, its precise role in atherogenesis and the underlying mechanisms have remained elusive. This study aimed to investigate the role of ASIC1 in atherosclerosis and its underlying mechanisms. First, data from a single-cell RNA sequencing (scRNA-seq) database were used to explore the relationships between ASIC1 differential expression and lipophagy in human atherosclerotic lesions. Finally, we validated the role of ASIC1/RIP1 signaling in lipophagy in vivo (human and mice) and in vitro (RAW264.7 and HTP-1 cells). Our results demonstrated a significant increase in ASIC1 protein levels within CD68+ macrophages in both human aortic lesions and AopE-/- mouse lesion areas compared to nonlesion regions. Concurrently, there was a notable decrease in lipophagy, a crucial process for lipid metabolism. In vitro assays further elucidated that ASIC1 interaction with RIP1 (receptor-interacting protein 1) promoted the phosphorylation of RIP1 at serine 166 and transcription factor EB (TFEB) at serine 142, leading to disrupted lipophagy and increased lipid accumulation. Intriguingly, all these events were reversed upon ASIC1 deficiency and RIP1 inhibition. Furthermore, in ApoE-/- mouse models of atherosclerosis, silencing ASIC1 expression or inhibiting RIP1 activation not only significantly attenuated atherogenesis but also restored TFEB-mediated lipophagy in aortic tissues. This was evidenced by reduced TFEB Ser-142 phosphorylation, decreased LC3II and LAMP1 protein expression, increased numbers of lipophagosomes, and a decrease in lipid droplets. Our findings unveil the critical role of macrophage ASIC1 in interacting with RIP1 to inhibit lipophagy, thereby promoting atherogenesis. Targeting ASIC1 represents a promising therapeutic avenue for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Glomerular lipid accumulation is a defining feature of diabetic kidney disease (DKD); however, the precise underlying mechanism requires further elucidation. Recent evidence suggests a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in intracellular lipid homeostasis. Although PCSK9 is present in kidneys, its role within kidney cells and relevance to renal diseases remain largely unexplored. Therefore, we investigated the role of intracellular PCSK9 in regulating lipid accumulation and homeostasis in the glomeruli and podocytes under diabetic conditions. Furthermore, we aimed to identify the pathophysiological mechanisms responsible for the podocyte injury that is associated with intracellular PCSK9-induced lipid accumulation in DKD. Methods: In this study, glomeruli were isolated from human kidney biopsy tissues, and glomerular gene-expression analysis was performed. Also, db/db and db/m mice were used to perform glomerular gene-expression profiling. We generated DKD models using a high-fat diet and low-dose intraperitoneal streptozocin injection in C57BL/6 and Pcsk9 knockout (KO) mice. We analysed cholesterol and triacylglycerol levels within the kidney cortex. Lipid droplets were evaluated using BODIPY staining. We induced upregulation and downregulation of PCSK9 expression in conditionally immortalised mouse podocytes using lentivirus and siRNA transfection techniques, respectively, under diabetic conditions. Results: A significant reduction in transcription level of PCSK9 was observed in glomeruli of individuals with DKD. PCSK9 expression was also reduced in podocytes of animals under diabetic conditions. We observed significantly higher lipid accumulation in kidney tissues of Pcsk9 KO DKD mice compared with wild-type (WT) DKD mice. Additionally, Pcsk9 KO mouse models of DKD exhibited a significant reduction in mitochondria number vs WT models, coupled with a significant increase in mitochondrial size. Moreover, albuminuria and podocyte foot process effacement were observed in WT and Pcsk9 KO DKD mice, with KO DKD mice displaying more pronounced manifestations. Immortalised mouse podocytes exposed to diabetic stimuli exhibited heightened intracellular lipid accumulation, mitochondrial injury and apoptosis, which were ameliorated by Pcsk9 overexpression and aggravated by Pcsk9 knockdown in mouse podocytes. Conclusions/interpretation: The downregulation of PCSK9 in podocytes is associated with lipid accumulation, which leads to mitochondrial dysfunction, cell apoptosis and renal injury. This study sheds new light on the potential involvement of PCSK9 in the pathophysiology of glomerular lipid accumulation and podocyte injury in DKD. [ABSTRACT FROM AUTHOR]

Abstract Background Obesity is a major contributing factor to the formation of gallstones. As early identification typically results in improved outcomes, we explored the relationship between visceral lipid accumulation indicators and the occurrence of gallstones. Methods This cross-sectional study involved 3,224 adults. The researchers employed multivariable logistic regression, smoothed curve fitting (SCF), threshold effects analysis, and subgroup analysis to examine the relationship between metabolic scores for visceral fat (METS-VF), waist circumference (WC), lipid accumulation products (LAP), and visceral adiposity index (VAI) and gallstones. A Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to identify key factors which were then used in the construction of a nomogram model. The diagnostic efficacy of this model in detecting gallstones was then determined using receiver operating characteristic curves. Results Visceral lipid accumulation indicators were strongly linked to the likelihood of having gallstones. Specific saturation effects for METS-VF, WC, LAP, and VAI and gallstones were determined using SCF. The inflection points for these effects were found to be 8.565, 108.400, 18.056, and 1.071, respectively. Subgroup analyses showed that associations remained consistent in most subgroups. The nomogram model, which was developed using critical features identified by LASSO regression, demonstrated excellent discriminatory ability, as indicated by an area under the curve value of 0.725. Conclusions Studies have shown that increases in METS-VF, WC, LAP, and VAI are linked to increased prevalences of gallstones. The nomogram model, designed with critical parameters identified using LASSO regression, exhibits a strong association with the presence of gallstones.

Abstract Scenedesmus sp. is a species of the Scenedesmus genus within the phylum Chlorophyta, commonly found as a planktonic algal species in freshwater and known for its rapid growth rate. This study employs room-temperature, atmospheric-pressure plasma mutagenesis for the breeding of Scenedesmus sp., utilizing transcriptomic analysis to investigate the biosynthesis mechanism of triglycerides. Further analysis of differentially expressed genes in transcriptome by measuring the macroscopic biological indicators of mutant and original algal strains. The findings of the study suggest that the mutant strain's photosynthesis has been enhanced, leading to improved light energy utilization and CO2 fixation, thereby providing more carbon storage and energy for biomass and lipid production. The intensification of glycolysis and the TCA (tricarboxylic acid) cycle results in a greater shift in carbon flux towards lipid accumulation. An elevated expression level of related enzymes in starch and protein degradation pathways may enhance acetyl CoA accumulation, facilitating a larger substrate supply for fatty acid production and thereby increasing lipid yield.

The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs. The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation. Fourteen pigs, including seven lean and seven obese pigs with body weights of approximately 80 kg, were fed the same diet at an amount approximately equivalent to 3% of their respective body weights daily for 42 d. In vitro, 3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium. Then, bile acids were added to mature adipocytes for 4 d. The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs (P

Introduction: Atherosclerosis, a major contributor to cardiovascular disease, remains a significant health concern worldwide. While previous research has shown that acid-sensing ion channel 1 (ASIC1) impedes macrophage cholesterol efflux, its precise role in atherogenesis and the underlying mechanisms have remained elusive. Objectives: This study aimed to investigate the role of ASIC1 in atherosclerosis and its underlying mechanisms. Methods: First, data from a single-cell RNA sequencing (scRNA-seq) database were used to explore the relationships between ASIC1 differential expression and lipophagy in human atherosclerotic lesions. Finally, we validated the role of ASIC1/RIP1 signaling in lipophagy in vivo (human and mice) and in vitro (RAW264.7 and HTP-1 cells). Result: Our results demonstrated a significant increase in ASIC1 protein levels within CD68+ macrophages in both human aortic lesions and AopE-/- mouse lesion areas compared to nonlesion regions. Concurrently, there was a notable decrease in lipophagy, a crucial process for lipid metabolism. In vitro assays further elucidated that ASIC1 interaction with RIP1 (receptor-interacting protein 1) promoted the phosphorylation of RIP1 at serine 166 and transcription factor EB (TFEB) at serine 142, leading to disrupted lipophagy and increased lipid accumulation. Intriguingly, all these events were reversed upon ASIC1 deficiency and RIP1 inhibition. Furthermore, in ApoE-/- mouse models of atherosclerosis, silencing ASIC1 expression or inhibiting RIP1 activation not only significantly attenuated atherogenesis but also restored TFEB-mediated lipophagy in aortic tissues. This was evidenced by reduced TFEB Ser-142 phosphorylation, decreased LC3II and LAMP1 protein expression, increased numbers of lipophagosomes, and a decrease in lipid droplets. Conclusion: Our findings unveil the critical role of macrophage ASIC1 in interacting with RIP1 to inhibit lipophagy, thereby promoting atherogenesis. Targeting ASIC1 represents a promising therapeutic avenue for the treatment of atherosclerosis.

This study is intended to explore the effect of hypoxia-inducible factor-1α (HIF-1α) activation on lipid accumulation in the diabetic kidney. A type 1 diabetic rat model was established by STZ intraperitoneal injection. Cobalt chloride (CoCl2) and YC-1 were used as the HIF-1α activator and antagonist, respectively. CoCl2 treatment significantly increased HIF-1α expression, accelerated lipid deposition, and accelerated tubular injury in diabetic kidneys. In vitro, CoCl2 effectively stabilized HIF-1α and increased its transportation from the cytoplasm to the nucleus, which was accompanied by significantly increased lipid accumulation in HK-2 cells. Furthermore, results obtained in vivo showed that HIF-1α protein expression in the renal tubules of diabetic rats was significantly downregulated by YC-1 treatment. Meanwhile, lipid accumulation in the tubules of the DM + YC-1 group was markedly decreased in comparison to the DM + DMSO group. Accordingly, PAS staining revealed that the pathological injury caused to the tubular epithelial cells was alleviated by YC-1 treatment. Furthermore, the blood glucose level, urine albumin creatinine ratio, and NAG creatinine ratio in the DM + YC-1 group were significantly decreased compared to the DM + DMSO group. Moreover, the protein expression levels of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) in diabetic kidneys were decreased by YC-1 treatment. Our findings demonstrate that the activation of HIF-1α contributed to interstitial injury in a rat model of diabetic nephropathy and that the underlying mechanism involved the induction of lipid accumulation. [ABSTRACT FROM AUTHOR]

Abstract Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Osteocalcin plays an important role in energy metabolism. In this study, we investigated the mechanism of action of chemically synthesized osteocalcin (csOCN) in ameliorating NAFLD. We demonstrated for the first time that csOCN attenuates lipid accumulation in the liver and hepatocytes by modulating CD36 protein expression. In addition, we found that the expression of p-AMPK, FOXO1 and BCL6 decreased and the expression of CD36 increased after OA/PA induction compared to the control group, and these effects were reversed by the addition of csOCN. In contrast, the therapeutic effect of csOCN was inhibited by the addition of AMPK inhibitors and BCL6 inhibitors. This finding suggested that csOCN regulates CD36 expression via the AMPK-FOXO1/BCL6 axis. In NAFLD mice, oral administration of csOCN also activated the AMPK pathway and reduced CD36 expression. Molecular docking revealed that osteocalcin has a docking site with CD36. Compared to oleic acid and palmitic acid, osteocalcin bound more strongly to CD36. Laser confocal microscopy results showed that osteocalcin colocalized with CD36 at the cell membrane. In conclusion, we demonstrated the regulatory role of csOCN in fatty acid uptake pathways for the first time; it regulates CD36 expression via the AMPK-FOXO1/BCL6 axis to reduce fatty acid uptake, and it affects fatty acid transport by may directly binding to CD36. There are indications that csOCN has potential as a CD36-targeted drug for the treatment of NAFLD.

Abstract Objectives Serum/glucocorticoid-inducible kinase 1 (SGK1) gene encodes a serine/threonine protein kinase that plays an essential role in cellular stress response and regulation of multiple metabolic processes. However, its role in bovine adipogenesis remains unknown. In this study, we aimed to clarify the role of SGK1 in bovine lipid accumulation and improvement of meat quality. Methods Preadipocytes were induced to differentiation to detect the temporal expression pattern of SGK1. Heart, liver, lung, spleen, kidney, muscle and fat tissues were collected to detect its tissue expression profile. Recombinant adenovirus and the lentivirus were packaged for overexpression and knockdown. Oil Red O staining, quantitative real-time PCR, Western blot analysis, Yeast two-hybrid assay, luciferase assay and RNA-seq were performed to study the regulatory mechanism of SGK1. Results SGK1 showed significantly higher expression in adipose and significantly induced expression in differentiated adipocytes. Furthermore, overexpression of SGK1 greatly promoted adipogenesis and inhibited proliferation, which could be shown by the remarkable increasement of lipid droplet, and the expression levels of adipogenic marker genes and cell cycle-related genes. Inversely, its knockdown inhibited adipogenesis and facilitated proliferation. Mechanistically, SGK1 regulates the phosphorylation and expression of two critical proteins of FoxO family, FOXO1/FOXO3. Importantly, SGK1 attenuates the transcriptional repression role of FOXO1 for PPARγ via phosphorylating the site S256, then promoting the bovine fat deposition. Conclusions SGK1 is a required epigenetic regulatory factor for bovine preadipocyte proliferation and differentiation, which contributes to a better understanding of fat deposition and meat quality improvement in cattle.

Abstract Background Evidence on the association between visceral lipid accumulation and infertility remains limited and controversial. Therefore, the current investigation is the first investigation to unveil this correlation by utilizing novel indicators of visceral lipid accumulation. Methods The present study utilized the NHANES 2013–2020 dataset. Researchers utilized multiple logistic regression, smoothed curve fitting, and subgroup analysis to investigate the associations of waist circumference (WC), metabolic score for visceral fat (METS-VF), lipid accumulation product (LAP), visceral adiposity index (VAI) with infertility. Additionally, the eXtreme Gradient Boosting (XGBoost) algorithm model was utilized to evaluate the relative importance of the factors. Results After adjusting for potential factors that could influence the results, researchers discovered that all these four indicators of visceral lipid accumulation exhibited strong positive correlations with the probability of infertility. The subgroup analysis demonstrated that the correlations remained consistent in the majority of subgroups (P for interaction > 0.05). The results of XGBoost algorithm model indicate that METS-VF is the most meaningful factor in infertility. The ROC curve research revealed that while METS-VF had the greatest AUC values, there was no variation in the AUC value of different markers of visceral fat accumulation (P > 0.05). Conclusions The present investigation discovered that increased WC, METS-VF, LAP, and VAI were associated with a heightened prevalence of infertility.

Glioblastoma-derived exosomes (GDEs), containing nucleic acids, proteins, fatty acids and other substances, perform multiple important functions in glioblastoma microenvironment. Tumor-derived exosomes serve as carriers of fatty acids and induce a shift in metabolism towards oxidative phosphorylation, thus driving immune dysfunction of dendritic cells (DCs). Lipid peroxidation is an important characteristic of ferroptosis. Nevertheless, it remains unclear whether GDEs can induce lipid accumulation and lipid oxidation to trigger ferroptosis in DCs. In our study, we investigate the impact of GDEs on lipid accumulation and oxidation in DCs by inhibiting GDEs secretion through knocking down the expression of Rab27a using a rat orthotopic glioblastoma model. The results show that inhibiting the secretion of GDEs can reduce lipid accumulation in infiltrating DCs in the brain and decrease mature dendritic cells (mDCs) lipid peroxidation levels, thereby suppressing glioblastoma growth. Mechanistically, we employed in vitro treatments of bone marrow-derived dendritic cells (BMDCs) withGDEs. The results indicate that GDEs decrease the viability ofmDCs compared to immature dendritic cells (imDCs) and trigger ferroptosis inmDCs via the NRF2/GPX4 pathway. Overall, these findings provide new insights into the development of immune-suppressive glioblastoma microenvironment through the interaction of GDEs with DCs. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that results in the elevation of serum ketone bodies, known as ketosis. This metabolic consequence has been suggested as a method for treating neurological conditions, improving exercise performance, and facilitating weight loss for overweight individuals. However, since most research primarily uses male populations, little is known about the potential sex differences during the consumption of the KD. In addition, the effects of the KD on aging are relatively unexplored. Therefore, the purpose of this study was to explore sex- and age-specific differences in mice fed the KD. Male and female C57BL/6N mice at either 12 wks or 24 wks of age were randomly assigned to a KD (90% fat, 1% carbohydrate) or chow (13% fat, 60% carbohydrate) group for 6 wks. KD induced weight gain, increased adiposity, induced hyperlipidemia, caused lipid accumulation in the heart and liver, and led to glycogen depletion in the heart, liver, and muscle with varying degrees of changes depending on age and sex. While younger and older male mice on the KD were prone to glucose intolerance, the KD acutely improved rotarod performance in younger females. Overall, this study highlights potential sex and aging differences in the adaptation to the KD. [ABSTRACT FROM AUTHOR]

Ethanol has been reported as a supplementary substrate for microalgae cultivation, however, information about its effect on the morphology, growth and desired metabolites accumulation of Chlorella sorokiniana is limited. To bridge this gap, the effects of exogenous ethanol on C. sorokiniana was screened by providing 0.00, 0.0025, 0.025, 0.1 and 1% (v/v) ethanol. Results showed ethanol caused multifaceted effects. 0.0025% and 0.025% ethanol caused a small increase in cell volume, growth and photosystem II (PSII) function. In contrast, cell volume conspicuously increased and was up to 2.5-fold (63.5 µm3) and 3.6-fold (91.3 µm3) higher in the 0.1% and 1% ethanol treatment groups, respectively, compared with the control (25.1 µm3). 1% ethanol conspicuously reduced chlorophyll concentration, inhibited growth, damaged the photosynthetic apparatus and decreased PSII electron transport. Carbohydrate and lipid accumulation increased in the 0.1% (112.6±7.8 µg mL-1) and 1% (217.87±31.6 µg mL-1) ethanol by 1.6 and 50-fold, compared to the control (70.5±2.2 µg mL-1and 7.2±2.6 µg mL-1). The cell permeability also increased coinciding with the pronounced increse of reactive oxygen species, particularly in the 0.1 and 1% ethanol treatment groups. There were giant palmloid-like cells containing unequal and numerous daughter cells in the higher ethanol treatments, indicating the cell cycle has been altered through suppression of mother cell cytokinesis, which could serve as a protective function to overcome ethanol stress. The results suggest that ethanol has the potential to be used as an impotent substrate to induce lipid and carbohydrate accumulation in C. sorokiniana cultivation. [ABSTRACT FROM AUTHOR]

Simple Summary: Castration induces fat deposition in boars and decreases carcass quality, prompting extensive research on the regulatory mechanism of fat deposition in castrated boars from a genetic perspective. Consequently, this study aimed to conduct a series of molecular biological experiments to elucidate how testosterone inhibits lipid droplet accumulation in porcine preadipocytes through ELOVL3. The findings from this study offer crucial data supporting genetic analyses of porcine fat deposition due to castration, thereby significantly contributing to enhancing pork quality and improving pig production efficiency. Castration is commonly used to reduce stink during boar production. In porcine adipose tissue, castration reduces androgen levels resulting in metabolic disorders and excessive fat deposition. However, the underlying detailed mechanism remains unclear. In this study, we constructed porcine preadipocyte models with and without androgen by adding testosterone exogenously. The fluorescence intensity of lipid droplet (LD) staining and the fatty acid synthetase (FASN) mRNA levels were lower in the testosterone-treated cells than in the untreated control cells. In contrast, the mRNA levels of adipose triglycerides lipase (ATGL) and androgen receptor (AR) were higher than in the testosterone-treated cells than in the control cells. Subsequently, transcriptomic sequencing of porcine preadipocytes incubated with and without testosterone showed that the mRNA expression levels of very long-chain fatty acid elongase 3 (ELOVL3), a key enzyme involved in fatty acids synthesis and metabolism, were high in control cells. The siRNA-mediated knockdown of ELOVL3 reduced LD accumulation and the mRNA levels of FASN and increased the mRNA levels of ATGL. Next, we conducted dual-luciferase reporter assays using wild-type and mutant ELOVL3 promoter reporters, which showed that the ELOVL3 promoter contained an androgen response element (ARE); furthermore, its transcription was negatively regulated by AR overexpression. In conclusion, our study reveals that testosterone inhibits fat deposition in porcine preadipocytes by suppressing ELOVL3 expression. Moreover, our study provides a theoretical basis for further studies on the mechanisms of fat deposition caused by castration. [ABSTRACT FROM AUTHOR]

Syrian hamsters are valuable models for studying lipid metabolism due to their sensitivity to dietary cholesterol, yet the precise impact of varying cholesterol levels has not been comprehensively assessed. This study examined the impact of varying dietary cholesterol levels on lipid metabolism in Syrian hamsters. Diets ranging from 0% to 1% cholesterol were administered to assess lipid profiles and oxidative stress markers. Key findings indicate specific cholesterol thresholds for inducing distinct lipid profiles: below 0.13% for normal lipids, 0.97% for elevated LDL-C, 0.43% for increased VLDL-C, and above 0.85% for heightened hepatic lipid accumulation. A cholesterol supplementation of 0.43% induced hypercholesterolemia without adverse liver effects or abnormal lipoprotein expression. Furthermore, cholesterol supplementation significantly increased liver weight, plasma total cholesterol, LDL-C, and VLDL-C levels while reducing the HDL-C/LDL-C ratio. Fecal cholesterol excretion increased, with stable bile acid levels. High cholesterol diets correlated with elevated plasma ALT activities, reduced hepatic lipid peroxidation, and altered leptin and CETP levels. These findings underscore Syrian hamsters as robust models for hyperlipidemia research, offering insights into experimental methodologies. The identified cholesterol thresholds facilitate precise lipid profile manipulation, enhancing the hamster's utility in lipid metabolism studies and potentially informing clinical approaches to managing lipid disorders. [ABSTRACT FROM AUTHOR]

Hepatic lipid metabolism is modulated by the circadian rhythm; therefore, circadian disruption may promote obesity and hepatic lipid accumulation. This study aims to investigate dietary pterostilbene (PSB) 's protective effect against high‐fat‐diet (HFD)‐induced lipid accumulation exacerbated by chronic jet lag and the potential role of gut microbiota therein. Mice were treated with a HFD and chronic jet lag for 14 weeks. The experimental group was supplemented with 0.25% (w/w) PSB in its diet to evaluate whether PSB had a beneficial effect. Our study found that chronic jet lag exacerbates HFD‐induced obesity and hepatic lipid accumulation, but these adverse effects were significantly mitigated by PSB supplementation. Specifically, PSB promoted hepatic lipolysis and β‐oxidation by upregulating SIRT1 expression, which indirectly reduced oxidative stress caused by lipid accumulation. Additionally, the PSB‐induced elevation of SIRT1 and SIRT3 expression helped prevent excessive autophagy and mitochondrial fission by activating Nrf2‐mediated antioxidant enzymes. The result was evidenced by the use of SIRT1 and SIRT3 inhibitors in in vitro studies, which demonstrated that activation of SIRT1 and SIRT3 by PSB is crucial for the translocation of PGC‐1α and Nrf2, respectively. Moreover, the analysis of gut microbiota suggested that PSB's beneficial effects were partly due to its positive modulation of gut microbial composition and functionality. The findings of this study suggest the potential of dietary PSB as a candidate to improve hepatic lipid metabolism via several mechanisms. It may be developed as a treatment adjuvant in the future. [ABSTRACT FROM AUTHOR]

Objectives: Serum/glucocorticoid-inducible kinase 1 (SGK1) gene encodes a serine/threonine protein kinase that plays an essential role in cellular stress response and regulation of multiple metabolic processes. However, its role in bovine adipogenesis remains unknown. In this study, we aimed to clarify the role of SGK1 in bovine lipid accumulation and improvement of meat quality. Methods: Preadipocytes were induced to differentiation to detect the temporal expression pattern of SGK1. Heart, liver, lung, spleen, kidney, muscle and fat tissues were collected to detect its tissue expression profile. Recombinant adenovirus and the lentivirus were packaged for overexpression and knockdown. Oil Red O staining, quantitative real-time PCR, Western blot analysis, Yeast two-hybrid assay, luciferase assay and RNA-seq were performed to study the regulatory mechanism of SGK1. Results: SGK1 showed significantly higher expression in adipose and significantly induced expression in differentiated adipocytes. Furthermore, overexpression of SGK1 greatly promoted adipogenesis and inhibited proliferation, which could be shown by the remarkable increasement of lipid droplet, and the expression levels of adipogenic marker genes and cell cycle-related genes. Inversely, its knockdown inhibited adipogenesis and facilitated proliferation. Mechanistically, SGK1 regulates the phosphorylation and expression of two critical proteins of FoxO family, FOXO1/FOXO3. Importantly, SGK1 attenuates the transcriptional repression role of FOXO1 for PPARγ via phosphorylating the site S256, then promoting the bovine fat deposition. Conclusions: SGK1 is a required epigenetic regulatory factor for bovine preadipocyte proliferation and differentiation, which contributes to a better understanding of fat deposition and meat quality improvement in cattle. [ABSTRACT FROM AUTHOR]

Simple Summary: The erucic acid (EA) present in rapeseed oil is known to inhibit growth and lipid utilization in terrestrial animals, but its potential anti-nutritional effects on fish have remained unclear due to a lack of information. Therefore, we conducted this study to investigate the effects of varying levels of EA on growth, health, and lipid metabolism in black carp, Mylopharyngodon piceus. The results demonstrated that high-dose EA inhibited growth, induced lipid accumulation, reduced antioxidant and immune capabilities, and led to oxidative damage by suppressing lipid catabolism and increasing lipogenesis. This study fills a gap in our understanding of the physiological and anti-nutritional effects of EA on fish and provides valuable theoretical insights for enhancing the utilization of rapeseed oil in cultured carnivorous fish. This study investigated the effects of dietary erucic acid (EA) on growth, lipid accumulation, antioxidant and immune abilities, and lipid metabolism in black carp fed six diets containing varying levels of EA (0.00%, 0.44%, 0.81%, 1.83%, 2.74%, and 3.49%), for 8 weeks. Results showed that fish fed the 3.49% EA diet exhibited lower weight gain, compared to those fed the 0.81% EA diet. In a dose-dependent manner, the serum triglycerides and total cholesterol were significantly elevated in the EA groups. The 1.83%, 2.74%, and 3.49% levels of EA increased alanine aminotransferase and aspartate aminotransferase activities, as well as decreased acid phosphatase and alkaline phosphatase values compared to the EA-deficient group. The hepatic catalase activity and transcriptional level were notably reduced, accompanied by increased hydrogen peroxide contents in the EA groups. Furthermore, dietary EA primarily increased the C22:1n-9 and C20:1n-9 levels, while decreasing the C18:0 and C18:1n-9 contents. In the EA groups, expressions of genes, including hsl, cpt1a, cpt1b, and ppara were downregulated, whereas the fas and gpat expressions were enhanced. Additionally, dietary EA elevated the mRNA level of il-1β and reduced the expression of il-10. Collectively, high levels of EA (2.74% and 3.49%) induced lipid accumulation, reduced antioxidative and immune abilities in black carp by inhibiting lipid catabolism and increasing lipogenesis. These findings provide valuable insights for optimizing the use of rapeseed oil rich in EA for black carp and other carnivorous fish species. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease worldwide. Caspase 8 and FADD-like apoptosis regulator (CFLAR) has been identified as a potent factor in mitigating non-alcoholic steatohepatitis (NASH) by inhibiting the N-terminal dimerization of apoptosis signal-regulating kinase 1 (ASK1). While arginine methyltransferase 1 (PRMT1) was previously reported to be associated with increased hepatic glucose production, its involvement in hepatic lipid metabolism remains largely unexplored. The interaction between PRMT1 and CFLAR and the methylation of CFLAR were verified by Co-IP and immunoblotting assays. Recombinant adenoviruses were generated for overexpression or knockdown of PRMT1 in hepatocytes. The role of PRMT1 in NAFLD was investigated in normal and high-fat diet-induced obese mice. In this study, we found a significant upregulation of PRMT1 and downregulation of CFLAR after 48h of fasting, while the latter significantly rebounded after 12h of refeeding. The expression of PRMT1 increased in the livers of mice fed a methionine choline-deficient (MCD) diet and in hepatocytes challenged with oleic acid (OA)/palmitic acid (PA). Overexpression of PRMT1 not only inhibited the expression of genes involved in fatty acid oxidation (FAO) and promoted the expression of genes involved in fatty acid synthesis (FAS), resulting in increased triglyceride accumulation in primary hepatocytes, but also enhanced the gluconeogenesis of primary hepatocytes. Conversely, knockdown of hepatic PRMT1 significantly alleviated MCD diet-induced hepatic lipid metabolism abnormalities and liver injury in vivo, possibly through the upregulation of CFLAR protein levels. Knockdown of PRMT1 suppressed the expression of genes related to FAS and enhanced the expression of genes involved in FAO, causing decreased triglyceride accumulation in OA/PA-treated primary hepatocytes in vitro. Although short-term overexpression of PRMT1 had no significant effect on hepatic triglyceride levels under physiological conditions, it resulted in increased serum triglyceride and fasting blood glucose levels in normal C57BL/6J mice. More importantly, PRMT1 was observed to interact with and methylate CFLAR, ultimately leading to its ubiquitination-mediated protein degradation. This process subsequently triggered the activation of c-Jun N-terminal kinase 1 (JNK1) and lipid deposition in primary hepatocytes. Together, these results suggested that PRMT1-mediated methylation of CFLAR plays a critical role in hepatic lipid metabolism. Targeting PRMT1 for drug design may represent a promising strategy for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Velvet antler, a traditional tonic widely used in East Asia for its health benefits, is explored in this study for its protective effects against hypoxia-induced damage using Caenorhabditis elegans (C. elegans) as a model. Hypoxia, characterized by low oxygen availability, induces significant physiological stress and potential tissue damage. Our research demonstrates that methanol extracts from velvet antler (MEs) enhance the survival of C. elegans under hypoxic conditions. This enhancement is achieved through the stabilization of hypoxia-inducible factor-1 (HIF-1) and the promotion of lipid accumulation, both of which are crucial for mitigating cellular damage. Specifically, MEs improve mitochondrial function, increase ATP production, and aid in the recovery of physical activity in C. elegans post-hypoxia or following hypoxia–reoxygenation (HR). The pivotal role of HIF-1 is underscored by the loss of these protective effects when HIF-1 function is inhibited. Additionally, our findings reveal that the gene related to lipid metabolism, ech-8, significantly contributes to the lipid accumulation that enhances resilience to hypoxia in C. elegans treated with MEs. These results not only highlight the therapeutic potential of velvet antler in modern medical applications, particularly for conditions involving hypoxic stress, but also provide insights into the molecular mechanisms by which MEs confer protection against hypoxic damage. [ABSTRACT FROM AUTHOR]

In this study, iron oxide nanoparticles (IONPs) were employed as an efficient chemical additive to enhance the Chlorella sp. biomass growth and lipid content. A novel strategy was developed to promote biomass growth and lipid content. Treatment with 20 mg/L followed by an additional 40 mg/L concentration of IONPs increased biomass and lipid content of Chlorella sp. by 53% and 67%, respectively, compared with the control. The hydrolyzate of 20 mg/L IONPs treated biomass residues obtained after combined hydrolysis showed maximum reducing sugars content of 41% dry cell weight (dcw), which was further used as substrate for dark fermentative hydrogen production mediated by Enterobacter aerogenes. The optimized concentration of IONPs supplementation in the dark fermentation system yielded 2.6 mol H 2 /mol sugar with acetate as predominant end metabolite. Hence, the present study demonstrated that the IONPs supplementation was a suitable chemical catalyst for biomass and biofuel production. [Display omitted] • 20 mg/L iron oxide nanoparticle supplementation enhances Chlorella sp. biomass • 60 mg/L iron oxide nanoparticle supplementation enhances Chlorella sp. lipid content • Biomass residues pretreated with combined hydrolysis produces 41% total reducing sugar • Iron oxide nanoparticle supplementation enhances dark fermentative hydrogen production • 30 mg/L iron oxide nanoparticle supplementation produces 2.6 mol H 2 /mol sugar [ABSTRACT FROM AUTHOR]

We confirmed that the hexane layer of Hydrangea macrophylla leaf extract (HLH) is rich in phyllodulcin (PD), an alternative sweetener, through high performance liquid chromatography (HPLC) analysis. To investigate in vivo activity of HLH and its PD, acute toxicity and growth rate of Caenorhabditis elegans were tested and there are no clinical abnormalities at 125-500 µg/mL of HLH. HLH decreased the total lipid and triglyceride contents dose-dependently in glucose-induced obese worms. Also, HLH increased survival rates under oxidative and thermal stress and decreased body reactive oxygen species (ROS) contents significantly. Such antioxidant properties of HLH were attributed to the enhanced activity of the antioxidant enzyme catalase. To determine whether the effect of HLH was due to PD, worms were treated with PD (concentration contained in HLH), and inhibitory effects on total lipids and ROS were observed. Our results suggest that HLH and its PD as a natural alternative sweetener can be used as materials to improve metabolic diseases. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effects of mitogen-inducible gene 6 (MIG6) overexpression on palmitic acid (PA)-induced endoplasmic reticulum stress-associated steatosis in hepatocytes. METHODS: A mouse model of nonalcoholic steatohepatitis was established by feeding twenty C57BL/6J mice a high-fat diet for 26 weeks. The mice were randomly divided into two groups: normal diet control group and high-fat diet group, and their livers were retained for subsequent experiments. The PA was used to induce lipid accumulation in HepG2 cells and AML12 cells, and the cells were divided into two groups: BSA (10% BSA) group and PA (500 μmol/L PA) group. The MIG6 overexpression was induced by transfecting HepG2 and AML12 cells with human and mouse MIG6 overexpression plasmids, respectively. The cells were divided into four groups according to their different treatment conditions: (1) negatiive+BSA group (transfected with negative control plasmid+10% BSA); (2) MIG6+BSA group (transfected with MIG6 overexpression plasmid+10% BSA); (3) negative+PA group (transfected with negative control plasmid+500 μmol/L PA); (4) MIG6+PA group (transfected with MIG6 overexpression plasmid+500 μmol/L PA). Lipid accumulation in hepatocytes was assessed by oil red O staining, and RT-qPCR was used to detect the mRNA expression level of MIG6 in liver tissues. The protein levels of MIG6, lipid synthesis-related molecules fatty acid synthase (FASN) and sterol regulatory element-binding protein 1 (SREBPl), and endoplasmic reticulum stress-related proteins glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in hepatocytes were detected using Western blot. RESULTS: High-fat diet increased the triglyceride content in the liver tissue of C57BL/6J mice induced lipid accumulation in hepatocytes and suppressed the mRNA expression level of MIG6 (P<0. 01). PA intervention increased the protein levels of lipid synthesis-related molecules such as FASN and SREBP1, and endoplasmic reticulum stress markers GRP78 and CHOP in hepatocytes, but inhibited MIG6 protein levels (P<0. 01). We transfected hepatocytes with MIG6 overexpression plasmid, which significantly increased MIG6 protein levels, decreased GRP78 and CHOP protein levels in hepatocytes (P<0. 01), significantly attenuated PA-induced lipid accumulation in hepatocytes, and down-regulated FASN and SREBP1 protein levels (P<0. 01). These results indicate that MIG6 overexpression inhibited PA-induced endoplasmic reticulum stress and attenuated lipid accumulation in hepatocytes. CONCLUSION: Overexpression of MIG6 inhibits lipid accumulation in hepatocytes by suppressing endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

• BMDMϕ engulf spinal cord debris, transform into proinflammatory foamy Mϕ in SCI. • Foamy Mϕ contribute to neuroinflammation and SCI progression. • ABCA1 deficiency in foamy Mϕ increases lipid accumulation and inflammation in SCI. • Enhancing ABCA1 inhibits the inflammation and rescues phagocytotic ability of Mϕ. • Enhancement of ABCA1 expression promotes lipid efflux and functional recovery. Spinal cord injury (SCI) triggers a complex cascade of events, including myelin loss, neuronal damage, neuroinflammation, and the accumulation of damaged cells and debris at the injury site. Infiltrating bone marrow derived macrophages (BMDMϕ) migrate to the epicenter of the SCI lesion, where they engulf cell debris including abundant myelin debris to become pro-inflammatory foamy macrophages (foamy Mϕ), participate neuroinflammation, and facilitate the progression of SCI. This study aimed to elucidate the cellular and molecular mechanisms underlying the functional changes in foamy Mϕ and their potential implications for SCI. Contusion at T10 level of the spinal cord was induced using a New York University (NYU) impactor (5 g rod from a height of 6.25 mm) in male mice. ABCA1, an ATP-binding cassette transporter expressed by Mϕ, plays a crucial role in lipid efflux from foamy cells. We observed that foamy Mϕ lacking ABCA1 exhibited increased lipid accumulation and a higher presence of lipid-accumulated foamy Mϕ as well as elevated pro-inflammatory response in vitro and in injured spinal cord. We also found that both genetic and pharmacological enhancement of ABCA1 expression accelerated lipid efflux from foamy Mϕ, reduced lipid accumulation and inhibited the pro-inflammatory response of foamy Mϕ, and accelerated clearance of cell debris and necrotic cells, which resulted in functional recovery. Our study highlights the importance of understanding the pathologic role of foamy Mϕ in SCI progression and the potential of ABCA1 as a therapeutic target for modulating the inflammatory response, promoting lipid metabolism, and facilitating functional recovery in SCI. [ABSTRACT FROM AUTHOR]

Positive remodeling is an integral part of the vascular adaptation process during the development of atherosclerosis, which can be detected by coronary computed tomography angiography (CTA). A total of 426 patients who underwent both coronary CTA and optical coherence tomography (OCT) were included. Four machine learning (ML) models, gradient boosting machine (GBM), random forest (RF), deep learning (DL), and support vector machine (SVM), were employed to detect specific plaque features. A total of 15 plaque features assessed by OCT were analyzed. The variable importance ranking was used to identify the features most closely associated with positive remodeling. In the variable importance ranking, lipid index and maximal calcification arc were consistently ranked high across all four ML models. Lipid index and maximal calcification arc were correlated with positive remodeling, showing pronounced influence at the lower range and diminishing influence at the higher range. Patients with more plaques with positive remodeling throughout their entire coronary trees had higher low-density lipoprotein cholesterol levels and were associated with a higher incidence of cardiovascular events during 5-year follow-up (Hazard ratio 2.10 [1.26–3.48], P ​= ​0.004). Greater lipid accumulation and less calcium burden were important features associated with positive remodeling in the coronary arteries. The number of coronary plaques with positive remodeling was associated with a higher incidence of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Evidence on the association between visceral lipid accumulation and infertility remains limited and controversial. Therefore, the current investigation is the first investigation to unveil this correlation by utilizing novel indicators of visceral lipid accumulation. Methods: The present study utilized the NHANES 2013–2020 dataset. Researchers utilized multiple logistic regression, smoothed curve fitting, and subgroup analysis to investigate the associations of waist circumference (WC), metabolic score for visceral fat (METS-VF), lipid accumulation product (LAP), visceral adiposity index (VAI) with infertility. Additionally, the eXtreme Gradient Boosting (XGBoost) algorithm model was utilized to evaluate the relative importance of the factors. Results: After adjusting for potential factors that could influence the results, researchers discovered that all these four indicators of visceral lipid accumulation exhibited strong positive correlations with the probability of infertility. The subgroup analysis demonstrated that the correlations remained consistent in the majority of subgroups (P for interaction > 0.05). The results of XGBoost algorithm model indicate that METS-VF is the most meaningful factor in infertility. The ROC curve research revealed that while METS-VF had the greatest AUC values, there was no variation in the AUC value of different markers of visceral fat accumulation (P > 0.05). Conclusions: The present investigation discovered that increased WC, METS-VF, LAP, and VAI were associated with a heightened prevalence of infertility. [ABSTRACT FROM AUTHOR]

Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid metabolism lead to pulmonary surfactant damage, resulting in hyperlipidemia in response to lung injury. Lung macrophages are responsible for recycling damaged lipid droplets to maintain lipid homeostasis. The inflammatory response triggered by external stimuli such as cigarette smoke, bleomycin, and bacteria can interfere with this process, resulting in the formation of lipid-laden macrophages (LLMs), also known as foamy macrophages. Recent studies have highlighted the potential significance of LLM formation in a range of pulmonary diseases. Furthermore, growing evidence suggests that LLMs are present in patients suffering from various pulmonary conditions. In this review, we summarize the essential metabolic and signaling pathways driving the LLM formation in chronic obstructive pulmonary disease, pulmonary fibrosis, tuberculosis, and acute lung injury. [ABSTRACT FROM AUTHOR]

Lipid-accumulated reactive astrocytes (LARAs) have recently been confirmed to be a pivotal cell type present in temporal lobe epilepsy (TLE) lesions. These cells not only induce anomalous lipid accumulation within the epileptic foci but also decrease the seizure threshold by employing upregulated activation of the adenosine A2A receptor (A2AR). Furthermore, disturbances in mitochondrial oxidative phosphorylation (OxPhos) have been noted as significant drivers of lipid accumulation in astrocytes. Moreover, the deficiency of OxPhos in astrocytes can induce severe neuroinflammation, which can worsen the progression of TLE. Accordingly, further exploration of the correlation between mitochondrial dysfunction, LARAs-mediated lipid accumulation, and A2AR activation within epilepsy lesions is warranted. It could potentially elucidate the vital role of mitochondrial dysfunction in the pathogenesis of TLE. [ABSTRACT FROM AUTHOR]

The past few decades have witnessed a rapid growth in the prevalence of nonalcoholic fatty liver disease (NAFLD). While the ketogenic diet (KD) is considered for managing NAFLD, the safety and efficacy of the KD on NAFLD has been a controversial topic. Here, we aimed to investigate the effect of KD of different durations on metabolic endpoints in mice with NAFLD and explore the underlying mechanisms. NAFLD mice were fed with KD for 1, 2, 4 and 6 weeks, respectively. The blood biochemical indexes (blood lipids, AST, ALT and etc.) and liver fat were measured. The LC–MS/MS based proteomic analysis was performed on liver tissues. Metallothionein-2 (MT2) was knocked down with adeno-associated virus (AAV) or small interfering RNA (siRNA) in NAFLD mice and AML-12 cells, respectively. H&E, BODIPY and ROS staining were performed to examine lipid deposition and oxidative stress. Furthermore, MT2 protein levels, nucleus/cytoplasm distribution and DNA binding activity of peroxisome proliferators-activated receptors α (PPARα) were evaluated. KD feeding for 2 weeks showed the best improvement on NAFLD phenotype. Proteomic analysis revealed that MT2 was a key candidate for different metabolic endpoints of NAFLD affected by different durations of KD feeding. MT2 knockdown in NAFLD mice blocked the effects of 2 weeks of KD feeding on HFD-induced steatosis. In mouse primary hepatocytes and AML-12 cells, MT2 protein levels were induced by β-hydroxybutyric acid (β-OHB). MT2 Knockdown blunted the effects of β-OHB on alleviating PA-induced lipid deposition. Mechanistically, 2 weeks of KD or β-OHB treatment reduced oxidative stress and upregulated the protein levels of MT2 in nucleus, which subsequently increased its DNA binding activity and PPARα protein expression. Collectively, these findings indicated that KD feeding prevented NAFLD in a time dependent manner and MT2 is a potential target contributing to KD improvement on steatosis. ▪ • KD prevents NAFLD phenotype in a time-dependent manner. • Two weeks of KD feeding is the optimal time point for alleviating NAFLD. • MT2 is a key effector of the temporal effect of KD. • MT2 reduces oxidative stress in livers of NAFLD mice. • MT2 increases the protein level and the DNA-binding activity of PPARα. [ABSTRACT FROM AUTHOR]

Abstract Pathological myopia (PM) is one of the leading causes of blindness, especially in Asia. To identify the genetic risk factors of PM, a two‐stage genome‐wide association study (GWAS) and replication analysis in East Asian populations is conducted. The analysis identified LILRB2 in 19q13.42 as a new candidate locus for PM. The increased protein expression of LILRB2/Pirb (mouse orthologous protein) in PM patients and myopia mouse models is validated. It is further revealed that the increase in LILRB2/Pirb promoted fatty acid synthesis and lipid accumulation, leading to the destruction of choroidal function and the development of PM. This study revealed the association between LILRB2 and PM, uncovering the molecular mechanism of lipid metabolism disorders leading to the pathogenesis of PM due to LILRB2 upregulation.

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key enzyme involved in the conversion of cortisone to active cortisol in the liver. Elevated cortisol levels can trigger oxidative stress, inflammation, and hepatocyte damage, highlighting the importance of 11β-HSD1 inhibition as a potential therapeutic approach. This study aimed to explore the effects of INU-101, an inhibitor of 11β-HSD1, on the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis. Our findings demonstrated that INU-101 effectively mitigated cortisol-induced lipid accumulation, reactive oxygen species generation, and hepatocyte apoptosis. Furthermore, 11β-HSD1 inhibition suppressed hepatic stellate cell activation by modulating β-catenin and phosphorylated SMAD2/3. INU-101 administration significantly reduced hepatic lipid accumulation and liver fibrosis in mice fed fast-food diet. This study suggests that INU-101 holds promise as a clinical candidate for treating MASLD and fibrosis, offering potential therapeutic benefits by targeting the intricate processes involving 11β-HSD1 and cortisol regulation in the liver.

The escalating prevalence of non-alcoholic fatty liver disease (NAFLD), driven by inadequate dietary habits and metabolic imbalances, underscores the urgent need for effective dietary interventions. This study investigated the potential of 80 % peanut diacylglycerol (DAG) as a functional lipid component in preventing NAFLD and associated intestinal microenvironment based on a high-cholesterol diet (HCD)-induced zebrafish model. We first found that the zebrafish fatty liver model shared multiple similar pathways like lipid-induced atherosclerosis, insulin resistance with NAFLD patient in terms of lipid metabolism. Employing larvae and grown zebrafish, we aimed to elucidate the preventive and alleviating effect of a DAG diet on NAFLD respectively. Results showed that DAG post-intervention significantly decreased hepatic lipid accumulation and diminished intestinal inflammatory in fatty liver zebrafish model. Notably, transcriptomic sequencing illuminated upregulation in genes related to lipid metabolism (e.g., fasn, mogat2, cd36), suggesting that peanut DAG accelerated lipid transportation and fostered a metabolic environment less conducive to NAFLD symptoms. Besides, reduced liver lipid droplets and hepatic inflammatory suggested DAG feeding could also prevent the formation of NAFLD. The study provided compelling evidence supporting the incorporation of DAG into the diet as a strategy for the prevention and management of fatty liver disease, proposing a novel approach to functional food development aimed at combating metabolic diseases.

Exposed to ubiquitously perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with non-alcoholic fatty liver disease (NAFLD), yet the underlying molecular mechanism remains elusive. The extrapolation of empirical studies correlating per- and polyfluoroalkyl substance (PFAS) exposure with NAFLD occurrence to real-life exposure was hindered by the limited availability of mechanistic data at environmentally relevant concentrations. Herein, a novel pathway mediating hepatocyte lipid accumulation by PFOA and PFOS at human-relevant dose (